Tailoring Multi-Phenyl Ring Cation for Stable Scalable Hybrid Bismuth Iodide Amorphous Film: Enabling Record Sensitivity and High-Performance X-Ray Array Imaging.

The 329-type bismuth (Bi)-based metal halide (MH) polycrystalline films have potential to be applied in the new generation of X-ray imaging technology owing to high X-ray absorption coefficients and excellent detection properties. However, the mutually independent [Bi2X9]3- units and numerous grain boundaries in the material lead to low carrier transport and collection capabilities, severe ion migration, large dark currents, and poor response uniformity. Here, a new multi-phenyl ring methyltriphenylphosphonium (MTP) is designed to optimize the energy band structure. For the first time, the coupling between the A-site cation and [Bi2X9]3- is realized, making it the main contributor to the conduction band minimum (CBM), getting rid of dilemma that carrier transport is confined to [Bi2X9]3-. Further, the preparation of MTP3Bi2I9 amorphous large-area wafer is achieved by melt-quenching; the steric hindrance effect improves stability, increases ion migration energy, and promotes response uniformity (14%). Moreover, the amorphous structure takes advantage of A-site cation participation in the conductivity, achieving a record sensitivity (7601 µC Gy-1 cm-2) and low dark current (≈0.11 nA) in the field of amorphous X-ray detection, and features low-temperature large-area preparation. Ultimately, designing amorphous array imaging devices that exhibit excellent response uniformity and potential imaging capabilities is succeeded here.

Upregulation of HAS2 promotes glioma cell proliferation and chemoresistance via c-myc.

Glioblastoma multiforme (GBM) is the most common and aggressive primary malignant human brain tumor. Although comprehensive therapies, including chemotherapy and radiotherapy following surgery, have shown promise in prolonging survival, the prognosis for GBM patients remains poor, with an overall survival rate of only 14.6 months. Chemoresistance is a major obstacle to successful treatment and contributes to relapse and poor survival rates in glioma patients. Therefore, there is an urgent need for novel strategies to overcome chemoresistance and improve treatment outcomes for human glioma patients. Recent studies have shown that the tumor microenvironment plays a key role in chemoresistance. Our study demonstrates that upregulation of HAS2 and subsequent hyaluronan secretion promotes glioma cell proliferation, invasion, and chemoresistance in vitro and in vivo through the c-myc pathway. Targeting HAS2 sensitizes glioma cells to chemotherapeutic agents. Additionally, we found that hypoxia-inducible factor HIF1α regulates HAS2 expression. Together, our findings provide insights into the dysregulation of HAS2 and its role in chemoresistance and suggest potential therapeutic strategies for GBM.

Analyzing the impacts of topographic factors and land cover characteristics on waterlogging events in urban functional zones.

Rapid urbanization and climate changes result in frequent occurrence of urban waterlogging disasters, which cause serious economic damage and pose a threat to residents' safety. Understanding the spatial characteristic and the key influencing factors of urban waterlogging has significant implications for mitigating waterlogging. In this study, the officially issued representative waterlogging points were obtained, as well as the topographic factors and land cover characteristics were selected to compare their impacts on the waterlogging event density in a highly urbanized area at urban functional zone (UFZ) scale, and to quantify the contributions of the key influencing factors on urban waterlogging events. Results showed the average density of urban waterlogging events in the study area is 9.2 points/km2, and 38.4 % of the waterlogging events are distributed in REZ. The distribution of waterlogging points in the study area revealed a significant multi-core and multilevel spatial aggregation pattern, and 12.1 % of the study area was high-density waterlogging area. In the total UFZs, the correlation coefficients of topographic indices with waterlogging density were relatively weaker than the other land cover characteristic metrics. The impervious surface ratio had significant contributions in all UFZ types. The larger ratio of impervious surface significantly increased the density of waterlogging events. The increase in the ratio of green space can effectively decrease the density of urban waterlogging. In the total UFZs, the top 3 key influencing factors of urban waterlogging were PR (35.9 %), COHESION (32.5 %) and DIVISION (11.8 %). The higher connectivity of landscape patches in REZ, INZ and COZ, as well as the increase of landscape dispersion or diversity in REZ, EGZ, INZ and GSZ can effectively reduce the occurrence of urban waterlogging. This study provides a better understanding of the formation mechanism of urban waterlogging disasters and potential implications for prioritized waterlogging mitigation strategies.

Pan-cancer analysis reveals the potential of hyaluronate synthase as therapeutic targets in human tumors.

Hyaluronic acid (HA) is a crucial component of the extracellular matrix, and its level of accumulation is related to the progression of various malignant tumors. In this study, a pan-cancer analysis of the three enzymes called hyaluronan synthases (HAS1, HAS2, and HAS3) that produce HA was performed. The study comprehensively describes the characteristics of HAS1, HAS2, and HAS3 in cancers using public databases and tools, to identify the potential biological pathways involved at the molecular, protein, cellular, and clinical sample levels. The analysis showed that dysregulation of the three genes often occurs in cancer, contributing to cancer progression, metastasis, and prognosis. Overexpression of HAS2 promotes secretion of HA in GBM and enhances cell proliferation and migration. The common and specific functions of HAS in certain diseases have important research implications for the treatment and prognosis of tumors.

Divergent response to abiotic factor determines the decoupling of water and carbon fluxes over an artificial C4 shrub in desert.

Knowledge on relationship and determinants of water and carbon dioxide (CO2) exchange is crucial to land managers and policy makers especially for the desertified land restoration. However, there remains highly uncertain in terms of water use and carbon sequestration for artificial plantation in desert. Here, continuous water and carbon fluxes were measured using eddy covariance (EC) in conjunction with hydrometeorological measurements over an artificial C4 shrub, Haloxylon ammodendron (C. A. Mey.) Bunge, from July 2020 to 2021 in Tengger Desert, China. Throughout 2021, evapotranspiration (ET) was 189.5 mm, of which 85% (150 mm) occurred during growing season, that was comparable with the summation of precipitation (132.2 mm), dew (33.5 mm) and potential other sources (e.g. deep subsoil water). This ecosystem was a strong carbon sink with net ecosystem production (NEP) up to 446.4 g C m-2 yr-1, much higher than surrounding sites. Gross primary production (GPP, 598.7 g C m-2 yr-1) in this shrubland was comparable with that of other shrublands, whereas ecosystem respiration (Re, 152.3 g C m-2 yr-1) was lower. Random Forest showed that environmental factors can explain 71.56% and 80.07% variation of GPP and ET, respectively. Interestingly, environmental factors have divergent effect on water and carbon exchange, i.e., soil hydrothermic factors (soil moisture content and soil temperature) determine the magnitude and seasonal pattern of ET and Re, while aerodynamics factors (net radiation, atmospheric temperature and wind speed) determine GPP and NEP. As such, divergent response of abiotic factors resulted in the decoupling of water and carbon exchange. Our results suggest that H. ammodendron is a suitable species for large-scale afforestation in dryland given its low water use but high carbon sequestration. Therefore, we infer that artificial planting H. ammodendron in dryland could provide an opportunity for climate change mitigation, and the long-term time series data is needed to confirm its sustainable role of carbon sequestration in the future.

Development and Determinants of Topsoil Bacterial and Fungal Communities of Afforestation by Aerial Sowing in Tengger Desert, China.

It was previously reported that afforestation in the desert can help improve soil texture, carbon accumulation, and nutrient status. However, the effects of afforestation on soil microbial composition, diversity, and microbial interactions with soil physicochemical properties have been rarely evaluated quantitatively. Using the method of space-for-time substitutions, we assessed the development and determinants of topsoil bacterial and fungal communities over nearly 40 years of successive afforestation by aerial sowing in Tengger Desert, China. The results showed that afforestation by aerial sowing comprised a considerable proportion of Chloroflexi and Acidobacteria in the bacterial community in addition to the ubiquitous phyla found in desert but had fewer effects on the dominant phyla of the fungal community. At the phylum level, the bacterial community was clearly clustered into two groups. However, it was difficult to differentiate the constituents of the fungal community based on principal coordinate analysis. The richness of the bacterial and fungal communities was significantly higher after five years than at zero years and three years. Additionally, the bacterial community varied parabolically and reached its largest size at twenty years, while the fungal community increased exponentially. Soil physicochemical properties were found to have divergent effects on the abundance and diversity of bacterial and fungal communities, among which salt- and carbon-associated properties (e.g., electrical conductivity, calcium, magnesium, total carbon, and organic carbon) were closely related with the abundance of bacterial-dominant phyla and the diversity of bacteria and fungi, but nutrient-associated properties (e.g., total phosphorus and available phosphorus) were not. The results indicate that afforestation through the salt secretions of plants leaves and carbon inputs from litter promote the development of topsoil bacterial and fungal communities in the desert.

Gelatin-based anticancer drug delivery nanosystems: A mini review.

Drug delivery nanosystems (DDnS) is widely developed recently. Gelatin is a high-potential biomaterial originated from natural resources for anticancer DDnS, which can effectively improve the utilization of anticancer drugs and reduce side effects. The hydrophilic, amphoteric behavior and sol-gel transition of gelatin can be used to fulfill various requirements of anticancer DDnS. Additionally, the high number of multifunctional groups on the surface of gelatin provides the possibility of crosslinking and further modifications. In this review, we focus on the properties of gelatin and briefly elaborate the correlation between the properties and anticancer DDnS. Furthermore, we discuss the applications of gelatin-based DDnS in various cancer treatments. Overall, we have summarized the excellent properties of gelatin and correlated with DDnS to provide a manual for the design of gelatin-based materials for DDnS.

Sensitive magnetic particle imaging of haemoglobin degradation for the detection and monitoring of intraplaque haemorrhage in atherosclerosis.

BACKGROUND: Intraplaque haemorrhage (IPH) drives atherosclerosis progression and is a key imaging biomarker of unstable plaques. Non-invasive and sensitive monitoring of IPH is challenging due to the compositional complexity and dynamic nature of atherosclerotic plaques. Magnetic particle imaging (MPI) is a highly sensitive, radiation-free, and no-tissue-background tomographic technique that detects superparamagnetic nanoparticles. Thus, we aimed to investigate whether MPI can in vivo detect and monitor IPH. METHODS: Thirty human carotid endarterectomy samples were collected and scanned with MPI. The tandem stenosis (TS) model was employed to establish unstable plaques with IPH in ApoE-/- mice. MPI and 7 T T1-weighted magnetic resonance imaging (MRI) were performed on TS ApoE-/- mice. Plaque specimens were analyzed histologically. FINDINGS: Human carotid endarterectomy samples exhibited endogenous MPI signals, which histologically colocalized with IPH. In vitro experiments identified haemosiderin, a haemoglobin degradation product, as a potential source of MPI signals. Longitudinal MPI of TS ApoE-/- mice detected IPH at unstable plaques, of which MPI signal-to-noise ratio values increased from 6.43 ± 1.74 (four weeks) to 10.55 ± 2.30 (seven weeks) and reduced to 7.23 ± 1.44 (eleven weeks). In contrast, 7 T T1-weighted MRI did not detect the small-size IPH (329.91 ± 226.82 µm2) at four weeks post-TS. The time-course changes in IPH were shown to correlate with neovessel permeability providing a possible mechanism for signal changes over time. INTERPRETATION: MPI is a highly sensitive imaging technology that allows the identification of atherosclerotic plaques with IPH and may help detect and monitor unstable plaques in patients. FUNDING: This work was supported in part by the Beijing Natural Science Foundation under Grant JQ22023; the National Key Research and Development Program of China under Grant 2017YFA0700401; the National Natural Science Foundation of China under Grant 62027901, 81827808, 81730050, 81870178, 81800221, 81527805, and 81671851; the CAS Youth Innovation Promotion Association under Grant Y2022055 and CAS Key Technology Talent Program; and the Project of High-Level Talents Team Introduction in Zhuhai City (Zhuhai HLHPTP201703).

Hydrocarbon Generation from Low-Mature Saline Lacustrine Sediments Studied Using Machine Learning and Chemometric Methods: The Succession of the Sikeshu Sag, Junggar Basin, NW China.

Significant attention has been given to the extensive development of saline environments in petroliferous basins. Further exploration and studies have discovered that saline environments, such as those for the deposition of source rocks in the Paleogene Anjihaihe (E2-3 a) Formation of the Sikeshu Sag, are ubiquitous in terrestrial lake basins. Previous studies have suggested that the oil reservoirs in the Sikeshu Sag and its peripheral regions are predominantly derived from the black mudstone and coal measures of the Lower Jurassic Badaowan (J1 b) Formation. However, with deeper exploration of the study area, a growing number of reservoirs with geochemical characteristics different from the J1 b oil source have been discovered, indicating that there are oil sources other than the J1 b source rocks. In this study, various machine learning algorithms were used (random forest, RF; convolutional neural networks, CNN; extreme gradient boosting, XGBoost; ElasticNetCV; Bayesian Ridge; and particle swarm optimization-support vector regression) to select the most suitable algorithm for predicting and comparing the quality of potential source rocks. A violin plot and Taylor diagram were applied to visually compare the reliability and application effectiveness of the models. The results demonstrated that XGBoost and RF can become essential tools for predicting the quality of potential source rocks. Moreover, the measured and predicted values of total organic carbon (TOC), hydrocarbon potential (S1 + S2), and hydrogen index indicate that there are three main source rocks: the E2-3 a, Lower Jurassic Sangonghe (J1 s), and J1 b formations. The thermal maturity of the E2-3 a source rocks is still early mature because of the saline-brackish water nature of these rocks, although large-scale hydrocarbon generation and expulsion can be achieved in the early mature stage. Based on their geochemical characteristics and stepwise discriminant analysis, the oils in the Sikeshu Sag and its peripheral regions can be categorized into two types: groups A and B. Comprehensive organic geochemical evidence suggests that genetically, group A oils are originated from E2-3 a less-mature saline lacustrine sedimentary rocks, while group B oils indicate similar affinity to the Jurassic source. Fluid inclusion microthermometry and one-dimensional basin modeling showed that the oil charging periods of group A and B oils were Middle-Late Miocene (13-8 Ma) and Late Oligocene (23-20 Ma), respectively. Quantitative grain fluorescence (QGF) analysis further propose that the hydrocarbon supply region of the E2-3 a sources is mainly located east of the Western Chepaizi Uplift and the interior area of the Sikeshu Sag, which breaks through the previous understanding that the Jurassic coal-derived oil source is the only main contributor in this study area. The research results can be widely applied to assess the petroleum resources of source rocks in similar areas worldwide.

Transcranial sonography with clinical and demographic characteristics to predict cognitive impairment in PD: a longitudinal study.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disease and is clinically characterized by a series of motor symptoms (MS) and nonmotor symptoms (NMS). NMS often appear before MS, while cognitive impairment mostly occurs within a few years after the diagnosis of PD. Therefore, we aimed to predict the risk factors for cognitive impairment (CI) in PD patients based on transcranial sonography, clinical symptoms, and demographic characteristics. METHODS: Based on the occurrence time of CI, a total of 172 PD patients were divided into non-CI (N-CI, n = 48), CI at the first treatment (F-CI, n = 58), and CI at the last treatment (L-CI, n = 66) groups. Clinical data (including MS and NMS) and ultrasonic data of all patients at the first treatment and the last treatment were collected retrospectively. Independent samples t tests were used to compare continuous data, and chi-square tests were used to compare categorical data. The risk factors for CI and Parkinson's disease dementia were identified by logistic regression analysis, and an ROC curve was established to explore the diagnostic efficacy. RESULTS: 1) The age of onset, first treatment and smoking history of CI patients were significantly different from those of N-CI patients. When age of first treatment ≥61 years was considered the boundary value to diagnose CI, the sensitivity and specificity were 77.40 and 66.70%, respectively. 2) The severity of depression was significantly different between F-CI and N-CI patients at the first treatment, while the cumulative and new or aggravated memory deficit was significantly different between the L-CI and N-CI patients at the last treatment. 3) There was a significant difference in TCS grading between the first and last treatment in L-CI patients. 4) Depression, sexual dysfunction, and olfactory dysfunction in NMS were independent risk factors for CI during the last treatment. 5) The sensitivity and specificity of predicting CI in PD patients were 81.80 and 64.60%, respectively. CONCLUSIONS: PD patients with CI were older, and most of them had a history of smoking. Furthermore, there was good diagnostic efficiency for predicting CI in PD via TCS combined with clinical characteristics (especially NMS).

A molecular probe carrying anti-tropomyosin 4 for early diagnosis of cerebral ischemia/reperfusion injury.

In vivo imaging of cerebral ischemia/reperfusion injury remains an important challenge. We injected porous Ag/Au@SiO2 bimetallic hollow nanoshells carrying anti-tropomyosin 4 as a molecular probe into mice with cerebral ischemia/reperfusion injury and observed microvascular changes in the brain using photoacoustic imaging with ultrasonography. At each measured time point, the total photoacoustic signal was significantly higher on the affected side than on the healthy side. Twelve hours after reperfusion, cerebral perfusion on the affected side increased, cerebrovascular injury worsened, and anti-tropomyosin 4 expression increased. Twenty-four hours after reperfusion and later, perfusion on the affected side declined slowly and stabilized after 1 week; brain injury was also alleviated. Histopathological and immunohistochemical examinations confirmed the brain injury tissue changes. The nanoshell molecular probe carrying anti-tropomyosin 4 has potential for use in early diagnosis of cerebral ischemia/reperfusion injury and evaluating its progression.

Imaging Guided Endogenic H2 -Augmented Electrochemo-Sonodynamic Domino Co-therapy of Tumor in Vivo.

Precise and on-demand release of sufficient hydrogen (H2 ) to tumor sites remains a key challenge for emerging H2 -oncotherapy, and little is known about the physiological effects of "abundant" H2 on complex tumor microenvironments (TME). Here, a highly efficient and cost-effective imaging-guided/-assessed H2 -therapy of tumors based on a joint electrochemo-sonodynamic treatment (H2 -EC/SD co-therapy) with strong "domino effect" triggered by endogenous H2 generation at tumor sites is reported to speedily eliminate tumor tissue (≤80 mm3 ) within 1 day. Adequate H2 is controllably generated in tumor sites through mild electrochemistry in vivo due to acidic TME by using clinical acupuncture Fe needles as electrodes. Besides starvation damage due to gas blockage/destruction of vessels, nano-/micro-bubbles of H2 formed in situ can elevate the tumor's internal temperature and burst vessels to further destroy the tumor under ultrasound irradiation. Remarkably, vulnerable homeostasis of TME is disturbed as H2 also participates in the physiological activity of tumor cells, leading to tumor dysfunction. Last but not least, the body's inflammatory response to cancer is reduced after the treatment, which is beneficial for the body's immune system during post-treatment recovery. Based on all of these merits, the H2 -EC/SD co-therapy provides a potentially safe and viable therapeutic strategy for future clinical applications.

Laser speckle contrast imaging for blood flow monitoring in predicting outcomes after cerebral ischemia-reperfusion injury in mice.

BACKGROUND: In the treatment of ischemic cerebral stroke (ICS), most conventional treatments, including carotid endarterectomy and carotid artery stenting, may cause cerebral ischemia-reperfusion injury (CIRI). For treated ICS patients, changes in cerebral blood flow are directly related to brain function. At present, computed tomography perfusion, dynamic susceptibility contrast-enhanced perfusion weighted imaging and magnetic resonance arterial spin labeling perfusion imaging are used to monitor cerebral blood flow, but they still have some limitations. Our study aimed to monitor the changes in cerebral cortical blood flow by laser speckle contrast imaging (LSCI) in CIRI model mice and to propose a new method for predicting outcomes after CIRI. C57BL/6 N mice were used to establish a mouse CIRI model based on a modified thread-occlusion method and divided into a good outcome group and a poor outcome group according to survival within 7 days. The cerebral cortical blood flow of the area supplied by the left middle cerebral artery was monitored by LSCI at baseline (before modeling), 1 h after ischemia, immediately after reperfusion and 24 h after reperfusion. Then, the brains of the mice were removed immediately and stained with hematoxylin and eosin to observe the pathological changes in brain neurons. RESULTS: The cerebral cortical blood flow in the poor outcome group was obviously reduced compared with that less in the good outcome group at 24 h after reperfusion (180.8 ± 20.9 vs. 113.9 ± 6.4, p = 0.001), and at 24 h after reperfusion, the cerebral cortical blood flow was negatively correlated with the severity of brain tissue injury (p = - 0.710, p = 0.010). CONCLUSIONS: LSCI can monitor the changes in cerebral cortical blood flow during CIRI in mice and could be used as a feasible method for predicting outcomes after CIRI in mice.

Experience in management of cesarean scar pregnancy and outcomes in a single center.

OBJECTIVE: This study aimed to describe our experience of managing cesarean scar pregnancy (CSP) and outcomes depending on ultrasound imaging features. METHODS: A retrospective, cohort observational study was performed on 31 consecutive patients with CSP at 6 to 9 weeks of gestation from April 2015 to January 2021. All patients were evaluated for the residual myometrial thickness (RMT), growth direction of the gestational sac (GS), blood flow, and chorionic parenchyma using ultrasonography. Patients underwent curettage or methotrexate (MTX) combined with curettage in CSP depending on the age of the GS. Blood loss of >500 mL with curettage was considered major bleeding. RESULTS: Twenty-five (80.6%) patients had successful treatment, and six (19.4%) patients had major bleeding. The incidence of major bleeding was significantly higher in patients with >7 weeks of gestation, types II and III CSP, mixed and exogenous types of the growth direction of the GS, an RMT < 2 mm, and multiple lacunae formation in thickened chorionic parenchyma. CONCLUSIONS: The exogenous and mixed types of the GS, an RMT < 2 mm, and multiple lacunae in thickened chorionic parenchyma may be high-risk factors for major hemorrhage by curettage in CSP.

Angioarchitectural Factors Associated with Postoperative Cerebral Infarction in Ischemic Moyamoya Disease.

OBJECTIVE: To investigate the angioarchitectural factors associated with postoperative cerebral infarction in ischemic moyamoya disease. METHODS: Data on patients who underwent surgery for ischemic MMD from 1 October 2015 to 31 October 2020, at Peking University International Hospital were collected and retrospectively analyzed. General conditions such as patient sex, age, site of surgery, preoperative manifestations such as TIA attack and old cerebral infarction, and seven angioarchitectural factors of the MMD based on DSA were selected and measured. Statistical analysis was performed by the Pearson chi-square statistic, analysis of variance (ANOVA), and multifactor logistic regression analysis. RESULTS: Age (OR, 0.969; 95%CI, 0.939-1.000; p = 0.049), A1stenosis (OR, 5.843; 95%CI, 1.730-19.732; p = 0.004), M1stenosis (OR, 6.206; 95%CI, 2.079-18.526; p = 0.001), PCA anomalies (OR, 4.367; 95%CI, 1.452-13.129; p = 0.049), Unstable compensation (OR, 5.335; 95%CI, 1.427-19.948; p = 0.013), TIA (OR, 4.264; 95%CI, 1.844-9.863; p = 0.001), Old cerebral infarction (OR, 2.972; 95%CI, 1.194-7.397; p = 0.019). The above seven factors can be used in the regression equation to predict the probability of postoperative cerebral infarction. The prediction accuracy is 90.2%. CONCLUSIONS: Age, TIA attack, old cerebral infarction, and five angioarchitectural factors of MMD are strongly associated with postoperative cerebral infarction. Seven factors, including age, TIA attack, old infarction, and four angioarchitectural factors, can be taken to quantify the probability of surgical cerebral infarction in MMD.

An in-plane supercapacitor obtained by facile template method with high performance Mn-Co sulfide-based oxide electrode.

Designing in-plane supercapacitors with high electrode materials selectivity is an indispensable approach to improve electrochemical performance. In this work, a facile template method was employed to fabricate in-plane supercapacitors. This template method could select any electrochemical active materials as electrode materials of in-plane supercapacitors. Hence, a high electrochemical performance material Mn-Co LDO-2S with optimized metal-sulfur bonds proportion and abundant sulfur vacancies was employed as electrode material of symmetrical in-plane supercapacitor (SPS). SPS exhibits excellent electrochemical performance finally, and has considerable area energy density 55.0µWh cm-2with an area power density of 0.7 mW cm-2. As a result, introducing sulfur atoms and sulfur vacancies are efficient approaches to improve electrode materials' electrochemical performance, and template method that proposed in this work is a promising approach to widen selectivity of in-plane supercapacitors' electrode materials.

Oral administration of Lactococcus lactis WHH2078 alleviates depressive and anxiety symptoms in mice with induced chronic stress.

Depression is a mood disorder with a high prevalence rate globally, which is associated with abnormalities in 5-hydroxytryptamine (5-HT) metabolism. Emerging evidence suggests that certain probiotics that modulate 5-HT metabolism confer beneficial effects on depression. In this study, in vitro enterochromaffin RIN14B cells were used for screening potential antidepressant probiotic Lactococcus lactis strains. The L. lactis strain WHH2078 increased to high levels the 5-HT precursor 5-hydroxytryptophan (5-HTP) and the expression of tryptophan hydroxylase 1 (Tph1), which converts tryptophan to 5-HTP in RIN14B cells. The oral administration of WHH2078 (1 × 109 CFU mL-1) in mice with induced chronic unpredictable mild stress (CUMS) for 5 weeks significantly ameliorated depressive and anxiety-like behaviors in the tail suspension test, forced swim test, sucrose preference test, and open field test. Besides, WHH2078 significantly reduced the serum corticosterone level and restored the central levels of 5-HT, 5-HTP, and brain-derived neurotrophic factor in CUMS-induced mice. Moreover, WHH2078 also reversed the 5-HTP levels in the serum and colon, accompanied by an upregulation in colonic Tph1 gene expression. Using 16S rRNA high-throughput sequencing of feces, WHH2078 was shown to improve the CUMS-induced gut microbial dysbiosis, through restoring alpha diversity and the abundances of Firmicutes and Bacteroidetes. In summary, these results indicate that WHH2078 can alleviate rodent depressive and anxiety-like behaviors in response to CUMS, which is associated with the improvement of 5-HT metabolism and modulation of the gut microbiome composition. Therefore, supplementation of the L. lactis strain WHH2078 with antidepressant properties may serve as a promising therapeutic strategy for chronic stress-induced depression.

Image-to-Images Translation for Multiple Virtual Histological Staining of Unlabeled Human Carotid Atherosclerotic Tissue.

PURPOSE: Histological analysis of human carotid atherosclerotic plaques is critical in understanding atherosclerosis biology and developing effective plaque prevention and treatment for ischemic stroke. However, the histological staining process is laborious, tedious, variable, and destructive to the highly valuable atheroma tissue obtained from patients. PROCEDURES: We proposed a deep learning-based method to simultaneously transfer bright-field microscopic images of unlabeled tissue sections into equivalent multiple sections of the same samples that are virtually stained. Using a pix2pix model, we trained a generative adversarial neural network to achieve image-to-images translation of multiple stains, including hematoxylin and eosin (H&E), picrosirius red (PSR), and Verhoeff van Gieson (EVG) stains. RESULTS: The quantification of evaluation metrics indicated that the proposed approach achieved the best performance in comparison with other state-of-the-art methods. Further blind evaluation by board-certified pathologists demonstrated that the multiple virtual stains have high consistency with standard histological stains. The proposed approach also indicated that the generated histopathological features of atherosclerotic plaques, such as the necrotic core, neovascularization, cholesterol crystals, collagen, and elastic fibers, are optimally matched with those of standard histological stains. CONCLUSIONS: The proposed approach allows for the virtual staining of unlabeled human carotid plaque tissue images with multiple types of stains. In addition, it identifies the histopathological features of atherosclerotic plaques in the same tissue sample, which could facilitate the development of personalized prevention and other interventional treatments for carotid atherosclerosis.

Biosynthetic Gas Vesicles Combined with Focused Ultrasound for Blood-Brain Barrier Opening.

Background: Focused ultrasound (FUS) combined with microbubbles (MBs) has emerged as a potential approach for opening the blood-brain barrier (BBB) for delivering drugs into the brain. However, MBs range in size of microns and thus can hardly extravasate into the brain parenchyma. Recently, growing attention has been paid to gas vesicles (GVs), which are genetically encoded gas-filled nanostructures with protein shells, due to their potential for extravascular targeting in ultrasound imaging and therapy. However, the use of GVs as agents for BBB opening has not yet been investigated. Methods: In this study, GVs were extracted and purified from Halobacterium NRC-1. Ultrasound imaging performance of GVs was assessed in vitro and in vivo. Then, FUS/GVs-mediated BBB opening for small molecular Evans blue or large molecular liposome delivery across the BBB was examined. Results: The results showed a good contrast performance of GVs for brain perfusion ultrasound imaging in vivo. At the acoustic negative pressure of 1.5 MPa, FUS/GVs opened the BBB safely, and effectively enhanced Evans blue and 200-nm liposome delivery into the brain parenchyma. Conclusion: Our study suggests that biosynthetic GVs hold great potential to serve as local BBB-opening agents in the development of new targeted drug delivery strategies for central nervous system disorders.